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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03292172




Registration number
NCT03292172
Ethics application status
Date submitted
20/09/2017
Date registered
25/09/2017
Date last updated
6/11/2020

Titles & IDs
Public title
A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer
Scientific title
Open Label, Dose Finding and Expansion Phase IB Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (Pd L1 Antibody) in Pateints With Advanced Ovarian Cancer or Triple Negative Breast Cancer
Secondary ID [1] 0 0
2017-001147-13
Secondary ID [2] 0 0
NP39487
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Ovarian Cancer 0 0
Triple Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - RO6870810

Experimental: Group 1 - Escalation Dose: RO6870810 + Atezolizumab - Participants will be administered escalating doses of RO6870810 (0.3 milligram per kilogram [mg/kg], 0.45 mg/kg, and 0.65 mg/kg) subcutaneously (SC) once daily (QD) along with fixed dose of atezolizumab 1200 mg intravenously (IV) on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.

Experimental: Group 2 - Sequential Dose: RO6870810 + Atezolizumab - Participants will be administered RO6870810 monotherapy (starting dose 0.30 mg/kg) during the first 14 days of 21-day Run-in period. Following the Run-in period, participants will continue to receive RO6870810 at the same dose in combination with fixed dose of atezolizumab 1200 mg IV every 3 weeks in 21-day cycles.

Experimental: Group 3 - Expansion in TNBC Group: RO6870810 + Atezolizumab - Participants will be administered dose of RO6870810 established in Group 1 (either 0.3 mg/kg, 0.45 mg/kg, or 0.65 mg/kg) SC QD along with fixed dose of atezolizumab 1200 mg IV on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.

Experimental: Group 4 - Expansion in OC Group: RO6870810 + Atezolizumab - Participants will be administered dose of RO6870810 established in Group 1 (either 0.3 mg/kg, 0.45 mg/kg, or 0.65 mg/kg) SC QD along with fixed dose of atezolizumab 1200 mg IV on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.


Treatment: Drugs: Atezolizumab
Atezolizumab will be given intravenously (IV) at a fixed dose of 1200 mg on Day 1 of each cycle, every 3 weeks.

Treatment: Drugs: RO6870810
RO6870810 will be injected SC,at initial planned doses of 0.30, 0.45, or 0.65 mg/kg, QD for the first 14 days of a 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Group 1: Percentage of Participants With Dose Limiting Toxicities (DLT)
Timepoint [1] 0 0
Cycle 1 (Day 21)
Primary outcome [2] 0 0
Groups 1 to 4: Percentage of Participants With Adverse Events (AEs)
Timepoint [2] 0 0
Up to 22 months
Primary outcome [3] 0 0
Groups 1 to 4: Percentage of Participants With Change in Vital Signs, Physical Findings, Electrocardiogram (ECG) and Laboratory Parameters
Timepoint [3] 0 0
Baseline up to follow-up visit (approximately 22 months)
Primary outcome [4] 0 0
Groups 3 and 4: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Timepoint [4] 0 0
From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Secondary outcome [1] 0 0
Groups 1 to 4: Maximum concentration (Cmax) of RO6870810 (RO) and Atezolizumab (Ate)
Timepoint [1] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [2] 0 0
Groups 1 to 4: Time of maximum concentration (tmax) of RO6870810 and Atezolizumab
Timepoint [2] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [3] 0 0
Groups 1 to 4: Clearance (CL) or Apparent Clearance (CL/F) of RO6870810 and Atezolizumab
Timepoint [3] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [4] 0 0
Groups 1 to 4: Volume of Distribution (Vd) or Apparent Volume of Distribution (Vd/F) of RO6870810 and Atezolizumab
Timepoint [4] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [5] 0 0
Groups 1 to 4: Area Under the Plasma Concentration-Time Curve From Time Zero to End of the Dosing Interval (AUC0-tau) of RO6870810 and Atezolizumab
Timepoint [5] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [6] 0 0
Groups 1 to 4: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6870810 and Atezolizumab
Timepoint [6] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [7] 0 0
Groups 1 to 4: Half life (t1/2) of RO6870810 and Atezolizumab
Timepoint [7] 0 0
RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Secondary outcome [8] 0 0
Groups 1 to 4: Trough concentration (Ctrough) of RO6870810 and Atezolizumab
Timepoint [8] 0 0
Pre-dose at Cycle 2 and at the beginning of every subsequent even-number cycles (Up to 22 months)
Secondary outcome [9] 0 0
Groups 1 and 2: Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Timepoint [9] 0 0
From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Secondary outcome [10] 0 0
Groups 1 to 4: Objective Response (OR) as per Immune-Modified RECIST
Timepoint [10] 0 0
From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Secondary outcome [11] 0 0
Groups 1 to 4: Duration of Response (DoR) as per RECIST v1.1 and Immune-Modified RECIST
Timepoint [11] 0 0
From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Secondary outcome [12] 0 0
Groups 1 to 4: Progression-Free Survival (PFS) per RECIST v1.1 and Immune-Modified RECIST
Timepoint [12] 0 0
From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Secondary outcome [13] 0 0
Groups 1 to 4: Overall Survival (OS)
Timepoint [13] 0 0
From the time of first dose of study treatment to the time of death from any cause (Up to 22 months)
Secondary outcome [14] 0 0
Groups 1 to 4: Tumor Marker Assessments (CA-125, According to Modified Gynecologic Cancer InterGroup [GCIG] Guidelines,CEA, CA15-3 Changes)
Timepoint [14] 0 0
Day 1 of each cycle till end of treatment or disease progression or death from any cause (Up to 22 months)
Secondary outcome [15] 0 0
Groups 1 to 4: Changes in CD11b Expression Levels Measurement in CD14+ Monocytes From Blood Association with Steady-State RO6870810 PK Drug Exposure
Timepoint [15] 0 0
Day 1, 8, 15, 21 of Run-in period , Cycle 1
Secondary outcome [16] 0 0
Groups 1 to 4: Changes in Markers (e.g., PD-L1, CD8/Ki 67) in Tissue Biopsy Specimens by Immunohistochemistry (IHC)
Timepoint [16] 0 0
Day 1, 15, 21 of Run-in period, Cycle 1
Secondary outcome [17] 0 0
Groups 1 to 4: Percentage of Participants With Transcript Profiling Assessment Receiving Combination Study Treatment
Timepoint [17] 0 0
Pre-dose Day 1, 21 Run-in period, Cycle 1; 6h post-dose Day 1 Run-in period, Cycle 1

Eligibility
Key inclusion criteria
-

- Groups 1 and 2: Participants with histologically confirmed advanced ovarian cancer or
triple negative breast cancer who in the opinion of the Investigator are appropriate
for this study

- Group 3: Participants with histologically confirmed TNBC who have received either one
or 2 prior systemic treatments for metastatic breast cancer, and who have documented
disease progression on or after the most recent treatment

- Group 4: Recurrent ovarian cancer participant who have received no more than two prior
lines of platinum therapy in the recurrent setting and have progressed within 9 months
from the last platinum containing regimen

- Measurable disease by RECIST criteria version 1.1 prior to study drug administration

- Performance status of 0 or 1 on the eastern Cooperative Oncology Group (ECOG) scale

- Life expectancy, in the opinion of the Investigator, of at least 3 months

- Disease-free of active second/secondary or prior malignancies for => 2 years with the
exception of squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
or breast

- Willing to provide the protocol specified tumor biopsies

- Acceptable hematologic status, liver and renal function

- Groups 1 and 2: Participants who have received prior treatment with CD137 agonists or
immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1
therapeutic antibodies, may be enrolled, provided the following requirements are met:

- Minimum of 5 months from the last dose of anti-PD-1, anti-CTLA-4, anti-PD- L1 or
CD137 agonist treatment

- No history of severe immune-related adverse effects from CD137 agonist,
anti-CTLA-4, anti-PD-1 or anti-PD-L1 (NCI CTCAE Grade 3 and 4). Any toxicity
related to the therapy must have resolved completely, no residual toxicity as
assessed by NCI CTCAE (v4.03)

- Agree to use protocol defined methods of contraception - For all participants, the
reliability of sexual abstinence must be evaluated in relation to the duration of the
clinical study and the preferred and usual lifestyle of the participant. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and
withdrawal are not acceptable methods of contraception
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants with history of prior malignancy except solid tumor treated curatively
more than 3 years ago without evidence of recurrence

- Asymptomatic or symptomatic, untreated, or actively progressing central nervous system
(CNS) metastases

- History of leptomeningeal disease

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures. Participants with indwelling catheters are allowed.

- Uncontrolled or symptomatic hypercalcemia

- New York Heart Association Class III or IV cardiac disease, pericarditis, myocardial
infarction within the past 6 months, unstable arrhythmia

- Fredericia-corrected QT interval (QTcF) > 470 milli seconds (msec) (female) or > 450
msec (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG)
abnormality, including pericarditis, which in the opinion of the Investigator would
preclude safe participation in the study.

- Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study
entry requiring systemic therapy. Participants with active TB infection are excluded
from the study.

- Known clinically important respiratory impairment

- History of major organ transplant

- History of an autologous or allogeneic bone marrow transplant

- Serious non-malignant disease that could compromise protocol objectives in the opinion
of the Investigator and/or the Sponsor

- Pregnant or nursing women

- Any systemic anticancer therapy within 3 weeks prior to Cycle 1 Day 1

- Any radiation treatment to metastatic site within <= 14 days of Cycle 1 Day 1

- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days
prior to Cycle 1 Day 1 or anticipation of need for major surgical procedure during the
course of the study

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric, human or humanized antibodies or fusion proteins

- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the atezolizumab formulation

- Active or history of autoimmune disease

- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan. History of radiation pneumonitis in the radiation field
(fibrosis) is permitted

- Positive test for Human immunodeficiency virus (HIV)

- Active hepatitis B or hepatitis C

- Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or
anticipation that such a live, attenuated vaccine will be required during the study

- Treatment with investigational therapy within 28 days prior to initiation of study
treatment

- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment

- Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the
first dose of study treatment and during the study

- Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the
first dose of study treatment and during the study

- Treatment with systemic immuno-stimulatory agents within 4 weeks or five half-lives of
the drug (whichever is shorter) prior to the first dose of study treatment

- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications within 2 weeks prior to the first dose of study treatment, or, anticipated
requirement for systemic immunosuppressive medications during the trial

- History of allergic reactions attributed to components of the formulated product(s)

- Unwillingness or inability to comply with procedures required in this protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/02/2019
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Oklahoma
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Denmark
State/province [5] 0 0
København Ø
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Edinburgh
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Manchester
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is Phase IB, open label, non-randomized study designed to investigate the dose, safety,
pharmacokinetics and anti-tumor activity of RO6870810 in combination with a fixed dose of
atezolizumab. The study consists of four groups, Group 1 (Dose Escalation Group) and Group 2
(Sequential Dose Group), and Groups 3 and 4 (Expansion Groups), which will further evaluate
the safety, pharmacokinetic, pharmacodynamic and preliminary clinical activity in patients
with triple negaive breast cancer and/or ovarian cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03292172
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03292172